Neoadjuvant chemotherapy has been extensively investigated in muscle-invasive bladder cancer. When taken together, the randomized controlled trials of neoadjuvant cisplatin-based combination chemotherapy demonstrate an improved survival over cystectomy alone. In addition, neoadjuvant chemotherapy can result in downstaging of primary tumors. As noted, a pT0 disease status at cystectomy is associated with a significant improvement in survival. A randomized controlled trial comparing neoadjuvant to adjuvant cisplatin-based chemotherapy shows that neither approach is superior. Finally, the ongoing EORTC/SWOG adjuvant chemotherapy trial, when completed, should add importantly to the literature concerning the role of systemic chemotherapy in muscle-invasive bladder cancer.